This research proposal will examine the relative roles of the vascular cell integrins alphavbeta3 and alphavbeta5 during cytokine- and tumor- induced angiogenesis and provide a framework for comparison of angiogenic cytokine expression and integrin-mediated neovascularization of various tumor types. Previous studies as well as preliminary data indicate that the vascular integrin alphavbeta3 is preferentially expressed in tissues undergoing active angiogenesis, and that specific antagonists of this receptor target newly forming blood vessels and block angiogenesis and tumor growth while leaving preexisting adjacent blood vessels unaffected. Furthermore, distinct angiogenic factors induce neovascularization by separate pathways susceptible to alphavbeta3- or alphavbeta5-specific antagonists. Therefore, I will analyze the relationship between these two pathways in angiogenesis induced by cytokines which specifically activate one pathway. In addition, tumor-induced neovascularization will be analyzed for the relative roles of these pathways and compared to the spectrum of angiogenic factor expression. I will further analyze the effects of alphavbeta3 and alphavbeta5 antagonists on the metastasis of tumor cells implanted on the chick CAM and within human skin transplants on the SCID mouse.